Guillain-Barré syndrome (GBS) is an immune-mediated disorder of the peripheral nervous system characterized by neuromuscular weakness and frequently accompanied by flaccid paralysis and may occasionally lead to death. It is classified as an acute inflammatory demyelinating polyneuropathy with a variant form designated as acute motor axonal neuropathy (Hughes and Cornblath, 2005. Lancet 366:1653-1666). Anti-ganglioside antibodies have been proposed as contributors to GBS pathogenesis (Kaida et al., 2009. J. Neuroimmunol. 182:212-218; Ariga and Yu, 2005. J. Neurosci. Res. 80:1-17). Gangliosides are abundantly expressed in human nerves (Yu et al., 2004. J. Lipid Res. 45:783-793) and generally believed to have important roles as mediators of cell adhesion and modulators of signal transduction (Regina Todeschini and Hakomori 2008. Biochim. Biophys. Acta 1780:421-433).
The etiology of GBS is complex and not fully known. A growing body of evidence, however, indicates that aberrant immune responses triggered by an infectious agent or vaccination allow disease development and the underlying pathogenetic mechanisms (Langmuir et al., 1984. Am J Epidemiol 119: 841-879; Kuwabara, 2004. Drugs 64: 597-610; Souayah et al., 2007. Vaccine 25: 5253-5255). The most commonly identified microbial agents are Campylobacter jejuni (C. jejuni), Haemophilus influenzae, cytomegalovirus (CMV), Epstein-Barr virus, and Mycoplasma pneumoniae (Hughes et al., 1999. J Neuroimmunol 100: 74-97; Hadden et al., 2001. Neurology 56: 758-765; Sivadon-Tardy et al., 2006. Emerg Infect Dis 12: 990-993; Sivadon-Tardy et al., 2009. Clin Infect Dis 48: 48-56). A preceding infectious event and patient-related host factors also seem to be related to certain subtypes of GBS and may affect the severity of the disease (Geleijns et al., 2005. Neurology 64: 44-49; Caporale et al., 2006. J Neuroimmunol 177: 112-118; Yuki, 2007. Muscle Nerve 35: 691-711.). C. jejuni infection frequently induces anti-ganglioside antibodies in the patient's serum (Yuki et al., 1990. Neurology 40: 1900-1902; Usuki et al., 2006. J Neurosci Res 83: 274-284). Thus, despite the possibility of other pathogenic mechanisms, an antibody-mediated process is one of the major insults to the nerve, causing both conduction block and velocity loss and the ensuing clinical symptoms (Rinaldi and Willison, 2008. Curr Opin Neurol 21: 540-546; van Doom et al., 2008. Lancet Neurol 7: 939-950; Kaida et al., 2009. Glycobiology 19: 676-692).
Conventional treatment strategies rely heavily on removal of pathogenic anti-glycolipid antibodies from the blood circulation. In practice, plasmapheresis and intravenous immunoglobulin (IVIG) have been used extensively for treatment (Buchwald et al., 2002. Ann Neurol 51: 673-680; Kieseier et al., 2008. Curr Opin Neurol 21: 555-562). Both strategies, however, are invasive and remove both nonpathogenic and pathogenic antibodies from circulation, with attendant risk of undesirable side effects.
It is an object of the invention to provide a methods and compositions for treating GBS with minimal or no side effects.